LETYBO
Generic: LETIBOTULINUMTOXINA-WLBG
Basic Information
Manufacturer
Hugel, Inc.
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
INTRAMUSCULAR
FDA Set ID
910e5d0e-4d0b-4de8-8e2d-97879a044181
Indications & Usage
1 INDICATIONS AND USAGE LETYBO is indicated for the temporary improvement in the appearance of moderate to severe glabellar lines associated with corrugator and/or procerus muscle activity in adult patients.
LETYBO is an acetylcholine release inhibitor and a neuromuscular blocking agent indicated for the temporary improvement in the appearance of moderate to severe glabellar lines associated with corrugator and/or procerus muscle activity in adult patients.
( 1 )
LETYBO is an acetylcholine release inhibitor and a neuromuscular blocking agent indicated for the temporary improvement in the appearance of moderate to severe glabellar lines associated with corrugator and/or procerus muscle activity in adult patients.
( 1 )
Adverse Reactions
6 ADVERSE REACTIONS The following serious adverse reactions are discussed in greater detail in other sections of the labeling: Spread of Toxin Effects [see Warnings and Precautions ( 5.1 )] Hypersensitivity Reactions [see Contraindications ( 4 ) and Warnings and Precautions ( 5.4 )] Cardiovascular System Adverse Reactions [see Warnings and Precautions ( 5.5 )] Increased Neuromuscular Compromise in Patients with Pre-Existing Neuromuscular Disorders [see Warnings and Precautions ( 5.6 )] Dysphagia and Dyspnea [see Warnings and Precautions ( 5.7 )] Ophthalmic Adverse Reactions in Patients Treated for Glabellar Lines [see Warnings and Precautions ( 5.9 )] The most common adverse reaction is headache (2%).
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact HUGEL at 1‑888-674-5355 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
In the three randomized, placebo-controlled, Phase 3 clinical trials that assess the use of LETYBO for the temporary improvement in the appearance of moderate to severe glabellar lines (BLESS I, II and III), 911 out of the 955 subjects who received a single dose treatment of 20 Units LETYBO and 310 out of the 317 subjects who received a single dose of placebo were included in safety analyses [see Clinical Studies ( 14 )] .
Table 2 lists the adverse reactions reported in more than one subject in the LETYBO group compared to the placebo in the placebo-controlled trials.
Most adverse reactions occur within the first week following injection of LETYBO and while generally transient, may have a duration of several months or longer.
Table 2: Adverse Reactions Reported in More Than One Subject in the LETYBO Group Compared to the Placebo Group in BLESS I, II and III Adverse Reaction Treatment LETYBO BLESS I, II, III N=911 n (%) PLACEBO BLESS I, II, III N=310 n (%) Headache* 17 (2%) 2 (1%) Brow ptosis** 3 (<1%) 0 Eyelid ptosis 3 (<1%) 0 Blepharospasm 2 (<1%) 0 * Includes headache, head discomfort, migraine, and procedural headache.
** Includes brow ptosis and brow heaviness.
The most frequently reported injection site reactions included administrative site swelling, facial pain, folliculitis, periorbital hematoma; and injection site bruising, reaction, pain, hematoma, nodule, pruritus, and mass.
BLESS I, II and III also included an open label, extension part with LETYBO.
The extension allowed subjects who had completed the double-blind portion of the trials to receive up to 3 additional elective LETYBO 20-Unit treatments for moderate to severe glabellar lines over a 48-week period.
Treatments were separated by at least a 3-month period.
Of the 1,129 subjects enrolled in the open label extension part of the trials, the median number of treatments was 3.
The adverse reaction profile was comparable to that reported in the randomized, single dose, double blind part of the trials.
Headache was the most common adverse reaction, reported in 2% of subjects, followed by injection site reactions (1%) [including contusion/bruising, administration site swelling, facial pain, periorbital hematoma, skin swelling; and injection site reaction, bruising, hematoma, mass, and nodule] and eyelid ptosis in 0.5% of subjects.
The incidence of these adverse reactions did not increase with multiple re-treatments.
6.2 Immunogenicity As with all therapeutic proteins, there is a potential for immunogenicity.
The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay.
Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease.
For these reasons, comparison of the incidence of antibodies to letibotulinumtoxinA-wlbg in the studies described below with the incidence of antibodies in other studies or to other products may be misleading.
Treatment with botulinum toxins may result in the formation of antibodies that may reduce the effectiveness of subsequent treatments by inactivating biological activity of the toxin.
Among 1,195 subjects treated with letibotulinumtoxinA-wlbg, four subjects (0.3%) developed antibodies to letibotulinumtoxinA-wlbg following treatment with LETYBO.
In the selected anti-drug antibodies positive samples that were further tested, there were no neutralizing anti-drug antibodies detected.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact HUGEL at 1‑888-674-5355 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
In the three randomized, placebo-controlled, Phase 3 clinical trials that assess the use of LETYBO for the temporary improvement in the appearance of moderate to severe glabellar lines (BLESS I, II and III), 911 out of the 955 subjects who received a single dose treatment of 20 Units LETYBO and 310 out of the 317 subjects who received a single dose of placebo were included in safety analyses [see Clinical Studies ( 14 )] .
Table 2 lists the adverse reactions reported in more than one subject in the LETYBO group compared to the placebo in the placebo-controlled trials.
Most adverse reactions occur within the first week following injection of LETYBO and while generally transient, may have a duration of several months or longer.
Table 2: Adverse Reactions Reported in More Than One Subject in the LETYBO Group Compared to the Placebo Group in BLESS I, II and III Adverse Reaction Treatment LETYBO BLESS I, II, III N=911 n (%) PLACEBO BLESS I, II, III N=310 n (%) Headache* 17 (2%) 2 (1%) Brow ptosis** 3 (<1%) 0 Eyelid ptosis 3 (<1%) 0 Blepharospasm 2 (<1%) 0 * Includes headache, head discomfort, migraine, and procedural headache.
** Includes brow ptosis and brow heaviness.
The most frequently reported injection site reactions included administrative site swelling, facial pain, folliculitis, periorbital hematoma; and injection site bruising, reaction, pain, hematoma, nodule, pruritus, and mass.
BLESS I, II and III also included an open label, extension part with LETYBO.
The extension allowed subjects who had completed the double-blind portion of the trials to receive up to 3 additional elective LETYBO 20-Unit treatments for moderate to severe glabellar lines over a 48-week period.
Treatments were separated by at least a 3-month period.
Of the 1,129 subjects enrolled in the open label extension part of the trials, the median number of treatments was 3.
The adverse reaction profile was comparable to that reported in the randomized, single dose, double blind part of the trials.
Headache was the most common adverse reaction, reported in 2% of subjects, followed by injection site reactions (1%) [including contusion/bruising, administration site swelling, facial pain, periorbital hematoma, skin swelling; and injection site reaction, bruising, hematoma, mass, and nodule] and eyelid ptosis in 0.5% of subjects.
The incidence of these adverse reactions did not increase with multiple re-treatments.
6.2 Immunogenicity As with all therapeutic proteins, there is a potential for immunogenicity.
The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay.
Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease.
For these reasons, comparison of the incidence of antibodies to letibotulinumtoxinA-wlbg in the studies described below with the incidence of antibodies in other studies or to other products may be misleading.
Treatment with botulinum toxins may result in the formation of antibodies that may reduce the effectiveness of subsequent treatments by inactivating biological activity of the toxin.
Among 1,195 subjects treated with letibotulinumtoxinA-wlbg, four subjects (0.3%) developed antibodies to letibotulinumtoxinA-wlbg following treatment with LETYBO.
In the selected anti-drug antibodies positive samples that were further tested, there were no neutralizing anti-drug antibodies detected.